The present invention relates to a process for the preparation of novel pyrimidine linked pyrrolo [2,1-c][1,4]benzodiazepines useful as potential antitumour agents. This invention also relates to a process for the preparation of new pyrimidine linked pyrrolo[2,1-c][1,4]benzodiazepines as potential antitumour agents. More particularly, it provides a process for the preparation of 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]alkoxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one with aliphatic chain length variations for the compounds and it also describes the anticancer (antitumour) activity. The structural formula of novel pyrrolo[2,1-c][1,4]benzodiazepine is as follows. 
Pyrrolo[2,1-c][1,4]benzodiazepines anti-tumour antibiotics are commonly known as anthramycin class of compounds. In the last few years, a growing interest has been shown in the development of new pyrrolo[2,1-c][1,4]benzodiazepines (PBDs). These antibiotics react covalently with DNA to form an N2-guanine adduct that lies within the minor groove of duplex DNA via an acid-labile aminal bond to the electrophilic imine at the N10-C11 position (Kunimoto, S.; Masuda, T.; Kanbayashi, N.; Hamada, M.; Naganawa, H.; Miyamoto, M.; Takeuchi, T.; and Unezawa, H. J. Antibiot., 1980, 33, 665.; Kohn, K. W. and Speous, C. L. J. Mol. Biol., 1970, 51, 551.; Hurley, L. H.; Gairpla, C. and Zmijewski, M. Biochem. Biophys. Acta., 1977, 475, 521.; Kaplan, D. J. and Hurley, L. H. Biochmestry, 1981, 20, 7572). The molecules have a right-handed twist, which allows them to follow the curvature of the minor groove of B-form double-stranded DNA spanning three base pairs. Recently, PBD dimers have been developed that comprises two C2-exo-methylene-substituted DC-81 subunits tethered through their C-8 position via an inert propanedioxy linker (Gregson, S. J.; Howard, P. W.; Hartely, J. A.; Brooks, N. A.; Adams, L. J.; Jenkins, T. C.; Kelland, L. R. and Thurston, D. E. J. Med. Chem. 2001, 44, 737). A recent development has been the linking of two PBD units through their C-8 positions to give bisfunctional alkylating agents capable of cross-linking DNA (Thurston, D. E.; Bose, D. S.; Thomson, A. S.; Howard, P. W.; Leoni, A.; Croker, S. J.; Jenkins, T. C.; Neidle, S. and Hurley, L. H. J. Org. Chem., 1996, 61, 8141-8147). Recently, a non-crassxe2x80x94linkingxe2x80x94mixed imine-amide PBD dimers have been synthesized which have significant DNA binding ability and potent anti tumour activitiy. (Kamal, A.; Ramesh, G.; Laxman, N.; Ramulu, p.; Srinivas, O.; Neelima, K.; Kumar, K. K.; Srinu, V. B.; Nagarajaram, H. M. J. Med. Chem. 2002, 45, 4679). 
Naturally occurring pyrrolo[2,1-c][1,4]benzodiazepines belong to a group of antitumour antibiotics derived from Streptomyces species. Recently, there is much impetus for the PBD systems as they can recognize and bind to specific sequence of DNA. Examples of naturally occurring PBD""s include anthramycin, DC-81, tomaymycin, sibiromycin and neothramycin. However, the clinical efficacy for these antibiotics is hindered by several limitations, such as poor water solubility and cardiotoxicity and development of drug resistance and metabolic inactivation.
The main object of the present invention is to provide new pyrrolo[2,1-c][1,4]benzodiazepines useful as antitumour agents.
Another object of the present invention is to provide a process for the preparation of novel pyrrolo[2,1-c][1,4]benzodiazepines useful as antitumour agents.
Accordingly the present invention provides a process for the preparation of a novel pyrrolo[2,1-c][1,4]benzodiazepine of formula VI wherein R=H, OH, OAc and n is 3-5. 
The present invention also provides a process for preparation of pyrrolo[2,1-c][1,4]benzodiazepines of formula VI above wherein R=H, OH, OAc and n is 3 to 5 which comprises reacting 6-4-(4-fluorophenyl)-2-methyl-4-pyrimidinol of formula I with dibromoalkanes in an aprotic water miscible organic solvents like acetone, THF and DMF in presence of mild inorganic bases like K2CO3, CsCO3 and BaCO3 upto refluxing temperature for a period up to 48 h, isolating n-bromoalkyl-6-(4-flurophenyl)-2-methyl-4-pyrimidinyl ether of formula II with (2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetal of formula III in presence of mild inorganic bases like K2CO3, CsCO3, and BaCO3 in presence of aprotic water miscible organic solvents up to refluxing for a period of 48 h isolating (2S)-N-[{4-[6xe2x80x3-(4xe2x80x2-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]alkoxy}-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxaldehyde diethyl thioacetal IV where n is 3 to 5 by conventional methods, reducing the above nitro compounds of formula IV with SnCl2.2H2O in presence of organic solvent up to a reflux temperature, isolating the (2S)-N-[{4-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]alkoxy}-5-methoxy-2-amonobenzoyl]pyrrolidine-2-carboxaldehyde diethyl thioacetal of formula V where n is 3 to 5 by known methods, reacting the above said amino compound of formula V with known deprotecting agents in a conventional manner to give novel pyrrolo[2,1-c][1,4]benzodiazepines of formula VI wherein n is as stated above.
The precursor, (2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetal of formula I (intermediates of DC-81) is prepared by literature methods (Thurston, D. E.; Murthy, V. S.; Langley, D. R.; Jones, G. B. Synthesis, 1990, 81)
Some representative compounds of formula VI present invention are given below:
1. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]propoxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one.
2. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]butoxy-(11aS)-1,2,3,11a-tetrahydro5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one.
3. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]pentoxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one.
4. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]propoxy-(4R)-hydroxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one
5. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]butoxy-(4R)-hydroxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one
6. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]pentoxy-(4R)-hydroxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one
7. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]propoxy-(4R)-acetyloxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one
8. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]butoxy-(4R)-acetyloxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one
9. 7-methoxy-8-[6xe2x80x2-(4xe2x80x3-fluorophenyl)-2xe2x80x2-methylpyrimidine-4xe2x80x2-yloxy]pentoxy-(4R)-acetyloxy-(11aS)-1,2,3,11a tetrahydro5H-pyrrolo[2,1,c][1,4]benzodiazepin-5-one.
These new analogues of pyrrolo[2,1-c][1,4]benzodiazepine hybrids linked at C-8 position have shown promising anticancer activity in various cell lines. The molecules synthesized are of immense biological significance with potential sequence selective DNA-binding property. This resulted in design and synthesis of new congeners as illustrated in Scheme-1, which comprise:
1. Ether linkage at C-8 position of DC-81 intermediates with pyrimidine ring moiety.
2. Refluxing the reaction mixture for 24-48 h.
3. Synthesis of C-8 linked PBD antitumour antibiotic hybrid imines.
4. Purification by column chromatography using different solvents like ethyl acetate, hexane, dichloromethane and methanol.